Competitive demethylation and substitution in N,N,N-trimethylanilinium fluorides

Haoran Sun, Stephen G. DiMagno

Research output: Contribution to journalArticlepeer-review

32 Scopus citations


Fluorination of aromatic compounds by nucleophilic displacement of trimethylanilinium salts by fluoride is a commonly used reaction for radiotracer synthesis. Though the liberated trimethylamine is thought to be an excellent leaving group for this type of SNAr reaction, scattered reports show that amine demethylation (reverse Menschutkin reaction) sometimes dominates over substitution, particularly when relatively electron rich fluoroarenes are the desired targets. Here we provide systematic experimental and theoretical studies of trimethylanilinium demethylation and substitution. Results from these studies highlight the limits of this leaving group in fluoroarene synthesis and have important ramifications for the design of nucleophilic fluorinating agents featuring ammonium cations.

Original languageEnglish (US)
Pages (from-to)806-812
Number of pages7
JournalJournal of Fluorine Chemistry
Issue number7
StatePublished - Jul 2007


  • Amine deprotection
  • Arene fluorination
  • Demethylation
  • Leaving groups
  • Nucleophilic substitution
  • PET
  • Reverse Menschutkin
  • S2
  • SAr
  • Tetrabutylammonium fluoride

ASJC Scopus subject areas

  • Biochemistry
  • Environmental Chemistry
  • Physical and Theoretical Chemistry
  • Organic Chemistry
  • Inorganic Chemistry


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